tbuckley/cabot-search huggingface dataset:
Group B Streptococcal Vaccine — Sisyphus Reconciled
Authors: Carol J. Baker
Journal: New England Journal of Medicine (2023)

As if envisioning the future dominance of group B streptococcus as a perinatal pathogen, Fry described the first well-characterized human infections 85 years ago in three postpartum London women with fatal disseminated septicemia.1 In the subsequent three decades, sporadic invasive group B streptococcal infections in parturients and neonates were described. However, in the 1970s, group B streptococcal disease dramatically changed when it emerged as the predominant cause of pneumonia, sepsis, and meningitis — often with fatal outcomes — in neonates and infants younger than 90 days of age. The incidence of maternal group B streptococcus–related complications, including intraamniotic infection, early . . .
The Metabolic Vulnerability Index
Authors: Katherine M. Conners, Joseph J. Shearer, Jungnam Joo, Hoyoung Park, Sheila M. Manemann, Alan T. Remaley, James D. Otvos, Margery A. Connelly, Maureen Sampson, Suzette J. Bielinski, Anna Wolska, Sarah Turecamo, Véronique L. Roger
Journal: JACC Heart Failure (2023)
Potential for Maternally Administered Vaccine for Infant Group B Streptococcus
Authors: Shabir A. Madhi, Annaliesa S. Anderson, Judith Absalon, David Radley, Raphael Simon, Babalwa Jongihlati, Renate Strehlau, Anika M. van Niekerk, Alane Izu, Niree Naidoo, Gaurav Kwatra, Yogandree Ramsamy, Mohamed Said, Stephanie Jones, Lisa Jose, Lee Fairlie, Shaun L. Barnabas, Ryan Newton, Samantha Munson, Zahra Jefferies, Danka Pavliakova, Natalie C. Silmon de Monerri, Emily Gomme, John L. Perez, Daniel A. Scott, William C. Gruber, Kathrin U. Jansen
Journal: New England Journal of Medicine (2023)

Natural history studies have correlated serotype-specific anti-capsular polysaccharide (CPS) IgG in newborns with a reduced risk of group B streptococcal disease. A hexavalent CPS-cross-reactive material 197 glycoconjugate vaccine (GBS6) is being developed as a maternal vaccine to prevent invasive group B streptococcus in young infants.
Prognostic Role of Early Cardiac Magnetic Resonance in Myocardial Infarction With Nonobstructive Coronary Arteries
Authors: Luca Bergamaschi, Alberto Foà, Pasquale Paolisso, Matteo Renzulli, Francesco Angeli, Michele Fabrizio, Lorenzo Bartoli, Matteo Armillotta, Angelo Sansonetti, Sara Amicone, Andrea Stefanizzi, Andrea Rinaldi, Fabio Niro, Luigi Lovato, Elisa Gherbesi, Stefano Carugo, Ferdinando Pasquale, Gianni Casella, Nazzareno Galiè, Paola Rucci, Chiara Bucciarelli-Ducci, Carmine Pizzi
Journal: JACC. Cardiovascular imaging (2023)
Anti-cyclic citrullinated peptide antibody and pain sensitisation in patients with rheumatoid arthritis: a cross-sectional analysis
Authors: Yoon Y Qiu, Tuhina Neogi, Lutfiyya N Muhammad, Jing Song, Marcy B Bolster, Wendy Marder, Andrew C Heisler, Alyssa Wohlfahrt, Dorothy Dunlop, Yvonne C Lee
Journal: Annals of the Rheumatic Diseases (2023)
AI-Guided Quantitative Plaque Staging Predicts Long-Term Cardiovascular Outcomes in Patients at Risk for Atherosclerotic CVD
Authors: Nick S. Nurmohamed, Michiel J. Bom, Ruurt A. Jukema, Robin J. de Groot, Roel S. Driessen, Pepijn A. van Diemen, Ruben W. de Winter, Emilie L. Gaillard, Ralf W. Sprengers, Erik S.G. Stroes, James K. Min, James P. Earls, Rhanderson Cardoso, Ron Blankstein, Ibrahim Danad, Andrew D. Choi, Paul Knaapen
Journal: JACC. Cardiovascular imaging (2023)

The recent development of artificial intelligence–guided quantitative coronary computed tomography angiography (CCTA) analysis (AI-QCT) has enabled rapid analysis of atherosclerotic plaque burden and characteristics. This study set out to investigate the 10-year prognostic value of atherosclerotic burden derived from AI-QCT and to compare the spectrum of plaque to manually assessed CCTA, coronary artery calcium scoring (CACS), and clinical risk characteristics. This was a long-term follow-up study of 536 patients referred for suspected coronary artery disease. CCTA scans were analyzed with AI-QCT and plaque burden was classified with a plaque staging system (stage 0: 0% percentage atheroma volume [PAV]; stage 1: >0%-5% PAV; stage 2: >5%-15% PAV; stage 3: >15% PAV). The primary major adverse cardiac event (MACE) outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, and all-cause mortality. The mean age at baseline was 58.6 years and 297 patients (55%) were male. During a median follow-up of 10.3 (IQR: 8.6-11.5) years, 114 patients (21%) experienced the primary outcome. Compared to stages 0 and 1, patients with stage 3 PAV and percentage of noncalcified plaque volume of >7.5% had a more than 3-fold (adjusted HR: 3.57; 95% CI 2.12-6.00; P < 0.001) and 4-fold (adjusted HR: 4.37; 95% CI: 2.51-7.62; P < 0.001) increased risk of MACE, respectively. Addition of AI-QCT improved a model with clinical risk factors and CACS at different time points during follow-up (10-year AUC: 0.82 [95% CI: 0.78-0.87] vs 0.73 [95% CI: 0.68-0.79]; P < 0.001; net reclassification improvement: 0.21 [95% CI: 0.09-0.38]). Furthermore, AI-QCT achieved an improved area under the curve compared to Coronary Artery Disease Reporting and Data System 2.0 (10-year AUC: 0.78; 95% CI: 0.73-0.83; P = 0.023) and manual QCT (10-year AUC: 0.78; 95% CI: 0.73-0.83; P = 0.040), although net reclassification improvement was modest (0.09 [95% CI: −0.02 to 0.29] and 0.04 [95% CI: −0.05 to 0.27], respectively). Through 10-year follow-up, AI-QCT plaque staging showed important prognostic value for MACE and showed additional discriminatory value over clinical risk factors, CACS, and manual guideline-recommended CCTA assessment.
Cluster Randomized Pragmatic Clinical Trial Testing Behavioral Economic Implementation Strategies to Improve Tobacco Treatment for Patients With Cancer Who Smoke
Authors: Brian P. Jenssen, Robert Schnoll, Rinad S. Beidas, Justin Bekelman, Anna-Marika Bauer, Sarah Evers-Casey, Tierney Fisher, Callie Scott, Jody Nicoloso, Peter Gabriel, David A. Asch, Alison M. Buttenheim, Jessica Chen, Julissa Melo, Dwayne Grant, Michael Horst, Randall Oyer, Lawrence N. Shulman, Alicia B.W. Clifton, Adina Lieberman, Tasnim Salam, Katharine A. Rendle, Krisda H. Chaiyachati, Rachel C. Shelton, Oluwadamilola Fayanju, E. Paul Wileyto, Sue Ware, Daniel Blumenthal, Daniel Ragusano, Frank T. Leone
Journal: Journal of Clinical Oncology (2023)

Few cancer centers systematically engage patients with evidence-based tobacco treatment despite its positive effect on quality of life and survival. Implementation strategies directed at patients, clinicians, or both may increase tobacco use treatment (TUT) within oncology.
Association between blood Loa loa microfilarial density and proteinuria levels in a rural area of the Republic of Congo (the MorLo project): a population-based cross-sectional study
Authors: Jérémy T Campillo, Marlhand C Hemilembolo, Sébastien D S Pion, Elodie Lebredonchel, Valentin Dupasquier, Charlotte Boullé, Ludovic G Rancé, Michel Boussinesq, François Missamou, Cédric B Chesnais
Journal: The Lancet Microbe (2023)

Case reports have hypothesised that proteinuria, sometimes with glomerulopathy or nephrotic syndromes, might be associated with loiasis. To our knowledge, no study has been done to assess this association. We aimed to investigate the association between Loa loa microfilariae burden and proteinuria.We did a cross-sectional study between May 16, 2022, and June 11, 2022, to assess the relationship between Loa loa microfilaraemia densities and proteinuria in a rural area of the Republic of Congo. We included all consenting adults living in the target area at study commencement who had L loa microfilarial densities greater than 500 microfilariae per mL during previous screening for a clinical trial in 2019. This study is part of the MorLo project, and used the project's study population of individuals aged 18 years or older who were living near Sibiti. For each microfilaraemic individual, two individuals without L loa microfilarial densities matched on age, sex, and place of residence were included. The association between proteinuria (assessed by dipstick) and L loa microfilarial densities, age, and sex was assessed using an unconstrained ordinal regression model since the parallel-lines assumption was violated for microfilarial densities.991 participants were included, of whom 342 (35%) were L loa microfilaraemic. The prevalence of microfilaraemia was 38% (122 of 325) among individuals with trace proteinuria (<300 mg/24 h), 51% (45 of 89) among individuals with light proteinuria (300 mg to 1 g/24 h), and 71% (15 of 21) among individuals with high proteinuria (>1 g/24 h). Individuals with high proteinuria had significantly higher L loa microfilarial densities (p<0·0001): mean microfilariae per mL were 1595 (SD 4960) among individuals with no proteinuria, 2691 (7982) for those with trace proteinuria, 3833 (9878) for those with light proteinuria, and 13 541 (20 118) for those with high proteinuria. Individuals with 5000-14 999 microfilariae per mL and individuals with 15 000 microfilariae per mL or greater were, respectively, 5·39 and 20·49 times more likely to have a high proteinuria than individuals with no microfilaraemia.The risk of proteinuria increases with L loa microfilaraemia. Further studies are needed to identify renal disorders (eg, tubulopathies, glomerulopathies, or nephrotic syndromes) responsible for loiasis-related proteinuria.European Research Council, MorLo project.For the French translation of the abstract see Supplementary Materials section.
Global access and patient safety in the transition to environmentally friendly respiratory inhalers: the Global Initiative for Asthma perspective
Authors: Mark L Levy, Eric D Bateman, Keith Allan, Leonard B Bacharier, Matteo Bonini, Louis-Philippe Boulet, Arnaud Bourdin, Chris Brightling, Guy Brusselle, Roland Buhl, Muhwa Jeremiah Chakaya, Alvaro A Cruz, Jeffrey Drazen, Francine M Ducharme, Liesbeth Duijts, Louise Fleming, Hiromasa Inoue, Fanny W S Ko, Jerry A Krishnan, Refiloe Masekela, Kevin Mortimer, Paulo Pitrez, Sundeep Salvi, Aziz Sheikh, Helen K Reddel, Arzu Yorgancıoğlu
Journal: The Lancet (2023)
Sex‐specific differences in myocardial injury incidence after <scp>COVID</scp>‐19 <scp>mRNA</scp>‐1273 booster vaccination
Authors: Natacha Buergin, Pedro Lopez‐Ayala, Julia R. Hirsiger, Philip Mueller, Daniela Median, Noemi Glarner, Klara Rumora, Timon Herrmann, Luca Koechlin, Philip Haaf, Katharina Rentsch, Manuel Battegay, Florian Banderet, Christoph T. Berger, Christian Mueller
Journal: European Journal of Heart Failure (2023)

To explore the incidence and potential mechanisms of oligosymptomatic myocardial injury following COVID-19 mRNA booster vaccination.Hospital employees scheduled to undergo mRNA-1273 booster vaccination were assessed for mRNA-1273 vaccination-associated myocardial injury, defined as acute dynamic increase in high-sensitivity cardiac troponin T (hs-cTnT) concentration above the sex-specific upper limit of normal on day 3 (48-96 h) after vaccination without evidence of an alternative cause. To explore possible mechanisms, antibodies against interleukin-1 receptor antagonist (IL-1RA), the SARS-CoV-2-nucleoprotein (NP) and -spike (S1) proteins and an array of 14 inflammatory cytokines were quantified. Among 777 participants (median age 37 years, 69.5% women), 40 participants (5.1%; 95% confidence interval [CI] 3.7-7.0%) had elevated hs-cTnT concentration on day 3 and mRNA-1273 vaccine-associated myocardial injury was adjudicated in 22 participants (2.8% [95% CI 1.7-4.3%]). Twenty cases occurred in women (3.7% [95% CI 2.3-5.7%]), two in men (0.8% [95% CI 0.1-3.0%]). Hs-cTnT elevations were mild and only temporary. No patient had electrocardiographic changes, and none developed major adverse cardiac events within 30 days (0% [95% CI 0-0.4%]). In the overall booster cohort, hs-cTnT concentrations (day 3; median 5, interquartile range [IQR] 4-6 ng/L) were significantly higher compared to matched controls (n = 777, median 3 [IQR 3-5] ng/L, p < 0.001). Cases had comparable systemic reactogenicity, concentrations of anti-IL-1RA, anti-NP, anti-S1, and markers quantifying systemic inflammation, but lower concentrations of interferon (IFN)-λ1 (IL-29) and granulocyte-macrophage colony-stimulating factor (GM-CSF) versus persons without vaccine-associated myocardial injury.mRNA-1273 vaccine-associated myocardial injury was more common than previously thought, being mild and transient, and more frequent in women versus men. The possible protective role of IFN-λ1 (IL-29) and GM-CSF warrant further studies.
Computational Reproducibility of Molecular Phylogenies
Authors: Sudhir Kumar, Qiqing Tao, Alessandra P Lamarca, Koichiro Tamura
Journal: Molecular Biology and Evolution (2023)

Repeated runs of the same program can generate different molecular phylogenies from identical data sets under the same analytical conditions. This lack of reproducibility of inferred phylogenies casts a long shadow on downstream research employing these phylogenies in areas such as comparative genomics, systematics, and functional biology. We have assessed the relative accuracies and log-likelihoods of alternative phylogenies generated for computer-simulated and empirical data sets. Our findings indicate that these alternative phylogenies reconstruct evolutionary relationships with comparable accuracy. They also have similar log-likelihoods that are not inferior to the log-likelihoods of the true tree. We determined that the direct relationship between irreproducibility and inaccuracy is due to their common dependence on the amount of phylogenetic information in the data. While computational reproducibility can be enhanced through more extensive heuristic searches for the maximum likelihood tree, this does not lead to higher accuracy. We conclude that computational irreproducibility plays a minor role in molecular phylogenetics.
Chemotherapy-induced reversal of ciltacabtagene autoleucel–associated movement and neurocognitive toxicity
Authors: Charlotte E. Graham, Won-Ho Lee, Hadley R. Wiggin, Valentina M. Supper, Mark B. Leick, Filippo Birocchi, Andrew J. Yee, Angelina Petrichenko, John Everett, Frederic D. Bushman, Hossein Sadrzadeh, Otto Rapalino, Daniel Chiu, Isabel Arrillaga-Romany, Marcela V. Maus, Matthew J. Frigault, Kathleen M. E. Gallagher
Journal: Blood (2023)
Association of Reducing the Recommended Colorectal Cancer Screening Age With Cancer Incidence, Mortality, and Costs in Canada Using OncoSim
Authors: Anastasia Kalyta, Yibing Ruan, Jennifer J. Telford, Mary A. De Vera, Stuart Peacock, Carl Brown, Fergal Donnellan, Sharlene Gill, Darren R. Brenner, Jonathan M. Loree
Journal: JAMA Oncology (2023)

Recent US guideline updates have advocated for colorectal cancer (CRC) screening to begin at age 45 years in average-risk adults, whereas Canadian screening programs continue to begin screening at age 50 years. Similarities in early-onset CRC rates in Canada and the US warrant discussion of earlier screening in Canada, but there is a lack of Canadian-specific modeling data to inform this.To estimate the association of a lowered initiation age for CRC screening by biennial fecal immunochemical test (FIT) with CRC incidence, mortality, and health care system costs in Canada.This economic evaluation computational study used microsimulation modeling via the OncoSim platform.Modeled rates of CRC incidence, mortality, and health care costs in Canadian dollars.This analysis included 4 birth cohorts (1973-1977, 1978-1982, 1983-1987, and 1988-1992) representative of the Canadian population accounting for previously documented effects of increasing CRC incidence in younger birth cohorts. Screening initiation at age 45 years resulted in a net 12 188 fewer CRC cases, 5261 fewer CRC deaths, and an added 92 112 quality-adjusted life-years (QALYs) to the cohort population over a 40-year period relative to screening from age 50 years. Screening initiation at age 40 years yielded 18 135 fewer CRC cases, 7988 fewer CRC deaths, and 150 373 QALYs. The cost per QALY decreased with younger birth cohorts to a cost of $762 per QALY when Canadians born in 1988 to 1992 began screening at age 45 years or $2622 per QALY with screening initiation at age 40 years. Although costs associated with screening and resulting therapeutic interventions increased with earlier screening, the overall health care system cost of managing CRC decreased.This economic evaluation study using microsimulation modeling found that earlier screening may reduce CRC disease burden and add life-years to the Canadian population at a modest cost. Guideline changes suggesting earlier CRC screening in Canada may be justified, but evaluation of the resulting effects on colonoscopy capacity is necessary.
Subtle Introgression Footprints at the End of the Speciation Continuum in a Clade of <i>Heliconius</i> Butterflies
Authors: Quentin Rougemont, Bárbara Huber, Simon H Martin, Annabel Whibley, Catalina Estrada, Darha Solano, Robert Orpet, W Owen McMillan, Brigitte Frérot, Mathieu Joron
Journal: Molecular Biology and Evolution (2023)

Abstract Quantifying gene flow between lineages at different stages of the speciation continuum is central to understanding speciation. Heliconius butterflies have undergone an adaptive radiation in wing color patterns driven partly by natural selection for local mimicry. Color patterns are also known to be used as assortative mating cues. Therefore, wing pattern divergence is considered to play a role in speciation. A corollary is that mimicry between closely related species may be associated with hybridization and interfere with reproductive isolation. Here, we take a multifaceted approach to explore speciation history, species boundaries, and traits involved in species differentiation between the two closely related species, Heliconius hecale and Heliconius ismenius. We focus on geographic regions where the two species mimic each other and contrast this with geographic regions where they do not mimic each other. To examine population history and patterns of gene flow, we tested and compared a four-population model accounting for linked selection. This model suggests that the two species have remained isolated for a large part of their history, yet with a small amount of gene exchange. Accordingly, signatures of genomic introgression were small except at a major wing pattern allele and chemosensing genes and stronger in the mimetic populations compared with nonmimetic populations. Behavioral assays confirm that visual confusion exists but that short-range cues determine strong sexual isolation. Tests for chemical differentiation between species identified major differences in putative pheromones which likely mediate mate choice and the maintenance of species differences.
Safety and efficacy of jaktinib (a novel JAK inhibitor) in patients with myelofibrosis who are intolerant to ruxolitinib: A single‐arm, open‐label, phase 2, multicenter study
Authors: Yi Zhang, Hu Zhou, Minghui Duan, Sujun Gao, Guangsheng He, Hongmei Jing, Junmin Li, Liangming Ma, Huanling Zhu, Chunkang Chang, Xin Du, Mei Hong, Xin Li, Qingchi Liu, Wei Wang, Na Xu, Haiping Yang, Binhua Lu, Hewen Yin, Liqing Wu, Shanshan Suo, Qingwei Zhao, Zhijian Xiao, Jie Jin
Journal: American Journal of Hematology (2023)

Although ruxolitinib improves splenomegaly and constitutional symptoms in patients with myelofibrosis (MF), a substantial proportion of patients discontinue ruxolitinib because of intolerance. This phase 2 trial investigated the safety and efficacy of jaktinib, a novel JAK inhibitor in patients with ruxolitinib-intolerant MF. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) at week 24. The secondary endpoints included change of MF-related symptoms, anemic response, and safety profiles. Between December 18, 2019, and November 24, 2021, 51 patients were enrolled, 45 treated with jaktinib 100 mg bid (100 mg bid group) and six received non-100 mg bid doses (non-100 mg bid group). The SVR35 at week 24 in the 100 mg bid group was 43.2% (19/44, 95% CI 29.7%-57.8%). There were 41.9% (13/31) of transfusion-independent patients with hemoglobin (HGB) ≤100 g/L who had HGB elevation ≥20 g/L within 24 weeks. The proportion of patients with a ≥50% decrease in the total symptom score (TSS 50) at week 24 was 61.8% (21/34). The most commonly reported grade ≥3 treatment-emergent adverse events (TEAEs) in the 100 mg bid group were anemia 31.1%, thrombocytopenia 22.2%, and infectious pneumonia 17.8%. A total of 16 (35.6%) in the 100 mg bid group had serious adverse events, and 4 (8.9%) were considered possibly drug related. These results indicate jaktinib can provide a treatment option for patients with MF who are intolerant to ruxolitinib.
A Single-Cell Taxonomy Predicts Inflammatory Niche Remodeling to Drive Tissue Failure and Outcome in Human AML
Authors: Lanpeng Chen, Eline Pronk, Claire van Dijk, Yujie Bian, Jacqueline Feyen, Tim van Tienhoven, Meltem Yildirim, Paola Pisterzi, Madelon M.E. de Jong, Alejandro Bastidas, Remco M. Hoogenboezem, Chiel Wevers, Eric M. Bindels, Bob Löwenberg, Tom Cupedo, Mathijs A. Sanders, Marc H.G.P. Raaijmakers
Journal: Blood Cancer Discovery (2023)

Abstract Cancer initiation is orchestrated by an interplay between tumor-initiating cells and their stromal/immune environment. Here, by adapted single-cell RNA sequencing, we decipher the predicted signaling between tissue-resident hematopoietic stem/progenitor cells (HSPC) and their neoplastic counterparts with their native niches in the human bone marrow. LEPR+ stromal cells are identified as central regulators of hematopoiesis through predicted interactions with all cells in the marrow. Inflammatory niche remodeling and the resulting deprivation of critical HSPC regulatory factors are predicted to repress high-output hematopoietic stem cell subsets in NPM1-mutated acute myeloid leukemia (AML), with relative resistance of clonal cells. Stromal gene signatures reflective of niche remodeling are associated with reduced relapse rates and favorable outcomes after chemotherapy across all genetic risk categories. Elucidation of the intercellular signaling defining human AML, thus, predicts that inflammatory remodeling of stem cell niches drives tissue repression and clonal selection but may pose a vulnerability for relapse-initiating cells in the context of chemotherapeutic treatment. Significance: Tumor-promoting inflammation is considered an enabling characteristic of tumorigenesis, but mechanisms remain incompletely understood. By deciphering the predicted signaling between tissue-resident stem cells and their neoplastic counterparts with their environment, we identify inflammatory remodeling of stromal niches as a determinant of normal tissue repression and clinical outcomes in human AML. See related commentary by Lisi-Vega and Méndez-Ferrer, p. 349. This article is featured in Selected Articles from This Issue, p. 337